A number of patents disclose certain N-phenyl-N-(4-alkoxyalkylpiperidin-4-yl)amides having therapeutic activity. For example, Janssen et al. U.S. Pat. No. 3,998,834 discloses certain N-phenyl-N-[(N-heterocyclic) piperidin-4-yl]amide compounds, useful as analgesics, having a 4-lower-alkoxy methyl substituent on the piperidine ring. Huang et al. U.S. Pat. No. 4,584,303 also discloses certain 4-alkoxyalkyl-substituted N-phenyl-N-[(N-heterocyclic)piperidin-4-yl]-amide compounds, useful as analgesics, having a 4-lower-alkoxy methyl substituent on the piperidine ring.
The 4-lower-alkoxy methyl piperdone ring substituent in these prior art compounds is introduced by reacting an appropriately N-substituted-4- piperidone compound with an appropriately substituted aniline compound and an alkali metal cyanide. The resulting nitrile derivative is then hydrolyzed to the corresponding amide, which in turn is hydrolyzed to the corresponding acid, which is then esterified, reduced with a hydride reagent to the corresponding alcohol, and subsequently O-alkylated.
Janssen, U.S. Pat. No. 3,164,600, discloses a process wherein N-benzylpiperidone is reacted with an arylamine to form a Schiff base compound which is reacted with an alkyl lithium to yield a 4-alkylpiperidine derivative. This method produces the desired alkylpiperidine compounds in low yields.
V. H. Rawal et al. disclose the use of the alpha-lithium derivative of methoxymethyl phenyl sulfide, [(methoxymethyl)-thio]benzene, as a synthetic reagent useful in adding to certain compounds containing a carbonyl group, a halide group, or an epoxide group, as well as to certain compounds containing a nitrile group, an amide group, or an acid chloride group, to form the corresponding acyl derivative compound, Synthetic Communications. 14, 1129-1139 (1984).